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The intertropical convergence zone (ITCZ), with its twice-annual passage over central Africa, is considered as the main driver of the rainfall seasonality. In this ITCZ paradigm, high rainfall occurs over regions of large low-level convergence. But recently, this paradigm was challenged over central Africa. Here, we show that a shallow meridional overturning circulation—driven by surface conditions—plays a thermodynamical control on the rainfall seasonality over central Africa. Indeed, due to the local evaporative cooling effect, the foot of the ascending branch of Hadley cells occurs where the temperature is the warmest, indicating a thermal low. This distorts the southern Hadley cell by developing its bottom-heavy structure. As result, both shallow and deep Hadley cells coexist over central Africa year-round. The deep mode is associated with the poleward transport of atmospheric energy at upper levels. The shallow mode is characterized by a shallow meridional circulation, with its moisture transport vanishing and converging in the midtroposphere rather than at lower troposphere. This midtropospheric moisture convergence is also the dominant component that shapes the vertically integrated moisture flux convergence, with little contribution of African easterly jets. This convergence zone thus controls the precipitating convection. Its meridional migration highlights the interhemispheric rainfall contrast over central Africa and outlines the unimodal seasonality. On the other hand, forced by the Congo basin cell, the precipitable water regulates the deep convection from the vegetated surface of Congo basin, acting as a continental sea. This nonlinear mechanism separates the rainfall into three distinct regimes: the moisture-convergence-controlled regime, with convective rainfall exclusively occurring in the rainy season; the local evaporation-controlled regime with drizzle in the dry season; and the precipitable-water-controlled regime, with exponential rainfall increase in the dry season.

Atmospheric circulation over central Africa is dominated by the tropical easterly jet, the African easterly jet, and the low-level westerly jet. In the lower troposphere, a zonal overturning cell occurs over central Africa, but the mechanisms driving its formation, seasonal evolution, and variability are still unclear. Here, using reanalyses (ERA-Interim, NCEP-2, and JRA-55) and the ECHAM5.3 atmospheric model forced by observed sea surface temperature, we highlight the existence, in the lower troposphere, of a separated single, closed, counterclockwise, and shallow zonal overturning cell, namely, the Congo basin cell. This Congo basin cell persists year round, with maximum intensity and width in August/September and minimum intensity and width in May. This shallow cell extracts heat from the warm central Africa landmass through latent and internal energies and transports it to the cold eastern equatorial Atlantic Ocean, reminiscent of the mixed Carnot–steam cycle. Indeed, the monsoon-like circulation triggered by the zonal surface pressure gradient between the warm central Africa landmass and surrounding cold oceans produces mass convergence at the Congo Air Boundary, providing necessary upward motion to air parcels to destabilize the atmosphere over central Africa. As result, convective updrafts depend on underlying moist static energy and the induced low-level westerly jet, controlled by the near-surface land–ocean thermal contrast through the zonal surface pressure gradient between the warm central African landmass and cold eastern equatorial Atlantic Ocean, rather than the midlevel easterly jet. This midlevel easterly jet is formed by the mechanical work that balances the convection associated with the saturation and rainfall. Furthermore, the efficiency of the Congo basin cell determines seasonality over central Africa.

10-year results from several studies showed improved disease-free survival and distant metastasis-free survival, reduced breast cancer-related mortality, and variable effects on overall survival with the addition of partial or comprehensive regional lymph node irradiation after surgery in patients with breast cancer. We present the scheduled 15-year analysis of the European Organisation for Research and Treatment of Cancer (EORTC) 22922/10925 trial, which aims to investigate the impact on overall survival of elective internal mammary and medial supraclavicular (IM-MS) irradiation. EORTC 22922/10925, a randomised, phase 3 trial done across 46 radiation oncology departments from 13 countries, included women up to 75 years of age with unilateral, histologically confirmed, stage I–III breast adenocarcinoma with involved axillary nodes or a central or medially located primary tumour. Surgery consisted of mastectomy or breast-conserving surgery and axillary staging. Patients were randomly assigned (1:1) centrally using minimisation to receive IM-MS irradiation at 50 Gy in 25 fractions (IM-MS irradiation group) or no IM-MS irradiation (control group). Stratification was done for institution, menopausal status, site of the primary tumour within the breast, type of breast and axillary surgery, and pathological T and N stage. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival analysed according to the intention-to-treat principle. Secondary endpoints were disease-free survival, distant metastasis-free survival, breast cancer mortality, any breast cancer recurrence, and cause of death. Follow-up is ongoing for 20 years after randomisation. This study is registered with ClinicalTrials.gov, NCT00002851. Between Aug 5, 1996, and Jan 13, 2004, we enrolled 4004 patients, of whom 2002 were randomly assigned to the IM-MS irradiation group and 2002 to the no IM-MS irradiation group. At a median follow-up of 15·7 years (IQR 14·0–17·6), 554 (27·7%) patients in the IM-MS irradiation group and 569 (28·4%) patients in the control group had died. Overall survival was 73·1% (95% CI 71·0–75·2) in the IM-MS irradiation group and 70·9% (68·6–72·9) in the control group (HR 0·95 [95% CI 0·84–1·06], p=0·36). Any breast cancer recurrence (24·5% [95% CI 22·5–26·6] vs 27·1% [25·1–29·2]; HR 0·87 [95% CI 0·77–0·98], p=0·024) and breast cancer mortality (16·0% [14·3–17·7] vs 19·8% [18·0–21·7]; 0·81 [0·70–0·94], p=0·0055) were lower in the IM-MS irradiation group than in the control group. No significant differences in the IM-MS irradiation group versus the control group were seen for disease-free survival (60·8% [95% CI 58·4–63·2] vs 59·9% [57·5–62·2]; HR 0·93 [95% CI 0·84–1·03], p=0·18), or distant metastasis-free survival (70·0% [67·7–72·2] vs 68·2% [65·9–70·3]; 0·93 [0·83–1·04], p=0·18). Causes of death between groups were similar. The 15-year results show a significant reduction of breast cancer mortality and any breast cancer recurrence by IM-MS irradiation in stage I–III breast cancer. However, this is not converted to improved overall survival. Ligue Nationale contre le Cancer and KWF Kankerbestrijding.

Discriminating climate impacts between 1.5 °C and 2 °C warming levels is particularly important for Central Africa, a vulnerable region where multiple biophysical, political, and socioeconomic stresses interact to constrain the region's adaptive capacity. This study uses an ensemble of 25 transient Regional Climate Model (RCM) simulations from the CORDEX initiative, forced with the Representative Concentration Pathway (RCP) 8.5, to investigate the potential temperature and precipitation changes in Central Africa corresponding to 1.5 °C and 2 °C global warming levels. Global climate model simulations from the Coupled Model Intercomparison Project phase 5 (CMIP5) are used to drive the RCMs and determine timing of the targeted global warming levels. The regional warming differs over Central Africa between 1.5 °C and 2 °C global warming levels. Whilst there are large uncertainties associated with projections at 1.5 °C and 2 °C, the 0.5 °C increase in global temperature is associated with larger regional warming response. Compared to changes in temperature, changes in precipitation are more heterogeneous and climate model simulations indicate a lack of consensus across the region, though there is a tendency towards decreasing seasonal precipitation in March-May, and a reduction of consecutive wet days. As a drought indicator, a significant increase in consecutive dry days was found. Consistent changes of maximum 5 day rainfall are also detected between 1.5 °C vs. 2 °C global warming levels.

Background Radiotherapy is considered as a second or third-line treatment for recurrent pituitary adenomas. As it is a benign tumor, the balance should clearly favor the benefit and induce the least amount of side effects. Purpose This retrospective study aims to evaluate the incidence of side effects after treatment and their actual causality with radiotherapy through dosimetric analysis. Methods A cohort of 35 patients who underwent normofractionated radiation therapy following unsuccessful surgical or medical interventions was identified. 48.6% (17/35) had functioning adenomas (29.41% adrenocorticotrophic hormone-secreting, 35.3% growth hormone-secreting, and 23.5% prolactin-secreting adenomas). Surgery was previously employed in 94.29% of patients. A median dose of 54 Gy was prescribed in the planning target volume (PTV) in a normofractionated schedule. Patients were clinically monitored by endocrinologists, ophthalmologists, and radiation oncologists, and patients underwent MRI and hormonal analyses frequently. Results The median follow-up time was 54.94 months. None of the patients experienced acute side effects of grade 3 or higher. Regarding late side effects, new-onset hypopituitarism was observed in 14.3% of patients, with all patients exceeding the dose constraint to pituitary gland. Additionally, 25.7% reported subjective memory loss complaints, 4 underwent a neuropsychological assessment, and only 2 were confirmed. Furthermore, 8 out of 9 patients did not adhere to the maximum dose constraints for the hippocampus. Subjective auditory impairment was experienced by 31.3% of patients, with 4 out of 11 undergoing ENT evaluation, and 1 out of 4 describing radio-induced tubal catharsis. All 11 patients adhered to the cochlear constraints. Five cases of cataracts were reported, with all patients adhering to lens constraints, although they were significantly older than those without cataracts. Two cases of temporary cranial nerve deficits, one visual impairment, one epilepsy, and one transient ischemic attack were also documented.

Radiotherapy delivered using photons induces an immune response that leads to modulation of the tumor microenvironment. Clinical studies are ongoing to evaluate immune checkpoint inhibitors in association with photon radiotherapy. At present, there is no publication on the radio-induced immune response after proton therapy. Balb/c mice bearing subcutaneous CT26 colon tumors were irradiated by a single fraction of 16.4 Gy using a proton beam extracted from a TR24 cyclotron. RNA sequencing analysis was assessed at 3 days post-treatment. Proton therapy immune response was monitored by flow cytometry using several panels (lymphoid, myeloid cells, lymphoid cytokines) at 7 and 14 days post-irradiation. RNA-Seq functional profiling identified a large number of GO categories linked to “immune response” and “interferon signaling”. Immunomonitoring evaluation showed induced tumor infiltration by immune cells. This is the first study showing the effect of proton therapy on immune response. These interesting results provide a sound basis to assess the efficacy of a combination of proton therapy and immune checkpoint inhibitors.

Background Radio(chemo)therapy is often required in pelvic malignancies (cancer of the anus, rectum, cervix). Direct irradiation adversely affects ovarian and endometrial function, compromising the fertility of women. While ovarian transposition is an established method to move the ovaries away from the radiation field, surgical procedures to displace the uterus are investigational. This study demonstrates the surgical options for uterine displacement in relation to the radiation dose received.  Methods The uterine displacement techniques were carried out sequentially in a human female cadaver to demonstrate each procedure step by step and assess the uterine positions with dosimetric CT scans in a hybrid operating room. Two treatment plans (anal and rectal cancer) were simulated on each of the four dosimetric scans (1. anatomical position, 2. uterine suspension of the round ligaments to the abdominal wall 3. ventrofixation of the uterine fundus at the umbilical level, 4. uterine transposition). Treatments were planned on Eclipse® System (Varian Medical Systems®,USA) using Volumetric Modulated Arc Therapy. Data about maximum (Dmax) and mean (Dmean) radiation dose received and the volume receiving 14 Gy (V14Gy) were collected. Results All procedures were completed without technical complications. In the rectal cancer simulation with delivery of 50 Gy to the tumor, Dmax, Dmean and V14Gy to the uterus were respectively 52,8 Gy, 34,3 Gy and 30,5cc (1), 31,8 Gy, 20,2 Gy and 22.0cc (2), 24,4 Gy, 6,8 Gy and 5,5cc (3), 1,8 Gy, 0,6 Gy and 0,0cc (4). For anal cancer, delivering 64 Gy to the tumor respectively 46,7 Gy, 34,8 Gy and 31,3cc (1), 34,3 Gy, 20,0 Gy and 21,5cc (2), 21,8 Gy, 5,9 Gy and 2,6cc (3), 1,4 Gy, 0,7 Gy and 0,0cc (4). Conclusions The feasibility of several uterine displacement procedures was safely demonstrated. Increasing distance to the radiation field requires more complex surgical interventions to minimize radiation exposure. Surgical strategy needs to be tailored to the multidisciplinary treatment plan, and uterine transposition is the most technically complex with the least dose received.

Background and objectiveIn breast cancer treatment, radiotherapy is an essential component for locoregional management. Axillary recurrence in patients with invasive breast carcinoma remains an issue. The question of whether breast irradiation may unintentionally include levels I, II, and III, and may decrease the risk of axillary recurrence, remains a topic of discussion.Patients and methodsA literature search was performed in PubMed and the Cochrane Library to identify articles that have published data regarding dose–volume analysis of axillary levels in breast irradiation. The following MESH terms were used: “breast cancer/lymph nodes” AND “radiotherapy dosage.”ResultsThirteen articles were identified. The irradiation technique, initial dose prescribed to the breast, delineated volumes, and dose received at axillary levels were heterogeneous. The average dose delivered to axilla levels I, II, and III with three-dimensional conformal radiotherapy using standard fields (ST) ranged between 22 and 43.5 Gy, 3 and 35.6 Gy, and 1.0 and 20.5 Gy, respectively. The average doses delivered to axilla levels I, II, and III with three-dimensional conformal radiotherapy using “high tangential” fields (HT) ranged between 38 and 49.7 Gy, 11 and 47.1 Gy, and 5 and 44.7 Gy, respectively. Finally, the average doses delivered to axilla levels I, II, and III using intensity-modulated radiation therapy (IMRT) were between 14.5 and 42.6 Gy, 3.4 and 35 Gy, and 1.2 and 25.5 Gy, respectively.ConclusionOur literature review suggests that the incidental dose delivered to the axilla during whole-breast irradiation is heterogenous and dependent on the irradiation technique used. However, whether this observation can be translated into a therapeutic effect is still a matter of debate.

The 2021 WHO glioma classification integrates molecular profiling, but outcome data for these patients are limited. We retrospectively analyzed 179 patients (median age 53) with WHO 2021-classified gliomas (grade 2: n = 45, grade 3: n = 51, grade 4: n = 83) treated with surgery and radio(chemo)therapy across four centers in Poland and France. Chemotherapy was administered to 74.9% of patients, with a median radiotherapy dose of 60 Gy (range 32.5–80 Gy). IDH1/2 mutations were identified in 55.3% and 1p/19q codeletion in 22.4%. Patients with IDH1/2 mutations had significantly longer progression-free survival (PFS, 7.7 vs. 1.0 years) and overall survival (OS, 8.2 vs. 2.5 years), both p  < 0.01. 1p/19q codeletion was associated with prolonged PFS (7.7 vs. 1.6 years, p  < 0.01). In grade 3 gliomas, chemotherapy improved PFS (6.8 vs. 3.6 years) and OS (6.9 vs. 3.9 years), both p  < 0.01. Leukopenia grade 0–2 correlated with better PFS (3.6 vs. 1.2 years, p = 0.02) and OS (7.2 vs. 3.2 years, p  = 0.04). Absolute lymphocyte count ≤ 1 × 10 3 /mm 3 predicted worse OS (5.3 vs. 8.7 years, p  = 0.0043). CTV < 127 cm 3 predicted longer OS in grade 4 gliomas (3.2 vs. 1.7 years, p  = 0.012). Our findings provide new real-world evidence on survival and prognostic factors in this population, for which contemporary RWE and OS/PFS data remain scarce.

CDKN2A is a tumor suppressor gene encoding the p16 protein, a key regulator of the cell cycle. CDKN2A homozygous deletion is a central prognostic factor for numerous tumors and can be detected by several techniques. This study aims to evaluate the extent to which immunohistochemical levels of p16 expression may provide information about CDKN2A deletion. A retrospective study was conducted in 173 gliomas of all types, using p16 IHC and CDKN2A fluorescent in situ hybridization. Survival analyses were performed to assess the prognostic impact of p16 expression and CDKN2A deletion on patient outcomes. Three patterns of p16 expression were observed: absence of expression, focal expression, and overexpression. Absence of p16 expression was correlated with worse outcomes. p16 overexpression was associated with better prognoses in MAPK-induced tumors, but with worse survival in IDH-wt glioblastomas. CDKN2A homozygous deletion predicted worse outcomes in the overall patient population, particularly in IDH-mutant 1p/19q oligodendrogliomas (grade 3). Finally, we observed a significant correlation between p16 immunohistochemical loss of expression and CDKN2A homozygosity. IHC has strong sensitivity and high negative predictive value, suggesting that p16 IHC might be a pertinent test to detect cases most likely harboring CDKN2A homozygous deletion.